---
_id: '4228'
abstract:
- lang: eng
  text: Suppressive drug interactions, in which one antibiotic can actually help bacterial
    cells to grow faster in the presence of another, occur between protein and DNA
    synthesis inhibitors. Here, we show that this suppression results from nonoptimal
    regulation of ribosomal genes in the presence of DNA stress. Using GFP-tagged
    transcription reporters in Escherichia coli, we find that ribosomal genes are
    not directly regulated by DNA stress, leading to an imbalance between cellular
    DNA and protein content. To test whether ribosomal gene expression under DNA stress
    is nonoptimal for growth rate, we sequentially deleted up to six of the seven
    ribosomal RNA operons. These synthetic manipulations of ribosomal gene expression
    correct the protein-DNA imbalance, lead to improved survival and growth, and completely
    remove the suppressive drug interaction. A simple mathematical model explains
    the nonoptimal regulation in different nutrient environments. These results reveal
    the genetic mechanism underlying an important class of suppressive drug interactions.
author:
- first_name: Tobias
  full_name: Bollenbach, Tobias
  last_name: Bollenbach
- first_name: Selwyn
  full_name: Quan, Selwyn
  last_name: Quan
- first_name: Remy P
  full_name: Remy Chait
  id: 3464AE84-F248-11E8-B48F-1D18A9856A87
  last_name: Chait
  orcid: 0000-0003-0876-3187
- first_name: Roy
  full_name: Kishony, Roy
  last_name: Kishony
citation:
  ama: Bollenbach T, Quan S, Chait RP, Kishony R. Nonoptimal Microbial Response to
    Antibiotics Underlies Suppressive Drug Interactions. <i>Cell</i>. 2009;139(4):707-718.
    doi:<a href="https://doi.org/10.1016/j.cell.2009.10.025">10.1016/j.cell.2009.10.025</a>
  apa: Bollenbach, T., Quan, S., Chait, R. P., &#38; Kishony, R. (2009). Nonoptimal
    Microbial Response to Antibiotics Underlies Suppressive Drug Interactions. <i>Cell</i>.
    Cell Press. <a href="https://doi.org/10.1016/j.cell.2009.10.025">https://doi.org/10.1016/j.cell.2009.10.025</a>
  chicago: Bollenbach, Tobias, Selwyn Quan, Remy P Chait, and Roy Kishony. “Nonoptimal
    Microbial Response to Antibiotics Underlies Suppressive Drug Interactions.” <i>Cell</i>.
    Cell Press, 2009. <a href="https://doi.org/10.1016/j.cell.2009.10.025">https://doi.org/10.1016/j.cell.2009.10.025</a>.
  ieee: T. Bollenbach, S. Quan, R. P. Chait, and R. Kishony, “Nonoptimal Microbial
    Response to Antibiotics Underlies Suppressive Drug Interactions,” <i>Cell</i>,
    vol. 139, no. 4. Cell Press, pp. 707–718, 2009.
  ista: Bollenbach T, Quan S, Chait RP, Kishony R. 2009. Nonoptimal Microbial Response
    to Antibiotics Underlies Suppressive Drug Interactions. Cell. 139(4), 707–718.
  mla: Bollenbach, Tobias, et al. “Nonoptimal Microbial Response to Antibiotics Underlies
    Suppressive Drug Interactions.” <i>Cell</i>, vol. 139, no. 4, Cell Press, 2009,
    pp. 707–18, doi:<a href="https://doi.org/10.1016/j.cell.2009.10.025">10.1016/j.cell.2009.10.025</a>.
  short: T. Bollenbach, S. Quan, R.P. Chait, R. Kishony, Cell 139 (2009) 707–718.
date_created: 2018-12-11T12:07:43Z
date_published: 2009-01-01T00:00:00Z
date_updated: 2021-01-12T07:55:27Z
day: '01'
doi: 10.1016/j.cell.2009.10.025
extern: 1
intvolume: '       139'
issue: '4'
month: '01'
page: 707 - 718
publication: Cell
publication_status: published
publisher: Cell Press
publist_id: '1890'
quality_controlled: 0
status: public
title: Nonoptimal Microbial Response to Antibiotics Underlies Suppressive Drug Interactions
type: journal_article
volume: 139
year: '2009'
...